Tissue reconstruction, regeneration of damaged tissues and organs, artificial organ production, and fabrication of living tissue constructs for proteomic, drug interaction, drug delivery, and pathogen analyses often requires the fabrication of tissue templates (scaffolds). Control over structure porosity in such scaffolds is critical. Precise control of scaffold porosity and internal pore architecture parameters (e.g. pore geometry, size, interconnectivity, orientation, and branching) is necessary to maximize nutrient diffusion, interstitial fluid and blood flow, to control cell growth and function, to manipulate tissue differentiation, and to optimize scaffold physical function and regenerated tissue physical properties.
The ability to manufacture with a range of materials and the ability to control the surface properties of the materials is also critical. The material employed allows control of scaffold degradation and mechanical integrity, cell interaction with the scaffold, and cell function. Material surface roughness, charge, hydrophobicity, and stability/dissolution have also been shown to regulate cell function.
Composites of polymer and ceramic are noteworthy because the mixed material composition can confer favorable mechanical properties, including strength via the ceramic phase, toughness and plasticity via the polymer phase, and graded mechanical stiffness. Biologic advantages include enhanced control over cell differentiation and the potential to deliver multiple biofactors, including growth factors, gene therapy vectors, and cells. Composite scaffolds may prove necessary for reconstruction of multi-tissue organs, tissue interfaces, and structural tissues including bone, cartilage, tendon, ligament and muscle.
However, the mechanical property requirements for hard tissue repair are difficult to satisfy using polymer/ceramic blend composites in which the ceramic and polymer components are mixed and occupy the same space. This is because large amounts of ceramic must be incorporated, making fabrication difficult. Therefore, composites with discrete regions of fully sintered HA are desirable for bone/soft tissue interfaces.
Composites scaffolds with discrete regions of materials are desirable for controlling structure mechanical properties, degradation kinetics, and biological interaction, as well as for producing structures that mimic natural tissue properties, structures that deliver several biofactors (drug/gene) vehicles, and living structures that contain multiple tissue components.
Although several manufacturing techniques exist to create scaffolds, precise control of pore geometry and interconnectivity is difficult. Conventional sponge scaffold manufacturing methods are capable of producing structures with locally-porous internal architectures from a diverse array of materials. The local pores in such scaffolds are voids characteristically defined by small struts and plates or spherical and tubular cavities generally less than 300 μm in diameter. These local pores are interconnected within local regions of the scaffold microstructure.
While these local pored scaffolds may include interconnected micro (less than 100 μm wide) pores that may comprise a continuous conduit throughout a scaffold, the pore connectivity is not an intentional result of an a priori global design. Rather, the connectivity is a random product of variable, local void interconnections that are affected by polymer processing parameters. Such random connections may not provide optimal scaffold permeability for tissue ingrowth nor optimal connectivity to maximize regenerated tissue mechanical properties.
Unlike sponge methods, micro-milling, textile, and direct solid free form (SFF) fabrication can be used to create scaffolds with good global pore control. The global pores take the shape of channels with non-random interconnectivity that are designed a priori to interconnect on a global scale across the scaffold. Unlike micro-milling and textile fabrication, full control over global pore architecture in 3D space is available with SFF. Unfortunately, the number of materials that can be used for each direct SFF manufacturing method is limited by the manufacturing process. Additionally, the incorporation of local pores in a direct SFF fabricated global pored scaffold is difficult.
Global and local pores are differentiated based on the extent of non-random designed interconnectivity. These pores may be sub-classified by size as either microporous (width less than 100 μm) or macroporous (width greater than 100 μm). Current direct SFF manufacturing is limited to manufacturing global pores with widths greater than 100 μm because of inherent limitations on the minimum size feature.
Direct SFF fabrication, also known as rapid prototyping, refers to a set of manufacturing processes that consists of building a 3D part in a layered fashion based on a computer representation. The part is often post processed (e.g. cleaning, curing, finishing) to yield the final product.
SFF has been used to mimic the 3D shape of macroscopic structures. However, a versatile method to manufacture biomimetic structures in the microscopic range, for example structures that mimic human trabecular bone or 3D vascular branching, has not been available. Such biomimetic strategies are desirable to replicate native tissue structure and function.
The need for 3D scaffolds with controlled local/global and micro/macro pores is great. However, current 3D local-pore scaffold fabrication methods do not allow fabrication of pores with designed geometry, orientation, branching, interconnectivity, and size. Global-pore manufacturing methods, including current SFF fabrication techniques, are not suitable for varied micro-pore structure fabrication and provide limited incorporation of local-pores within a global-porous structure. Additionally, the need for 3D scaffolds made from a variety of materials is great. Further, control over the discrete spatial location and surface properties of varied materials within the same scaffold is desired.